What's the Risk? Older Women Report Fewer Symptoms for Suspected Acute Coronary Syndrome than Younger Women.

The purpose of the study was to determine whether older (≥65 years) and younger (<65 years) women presenting to the emergency department (ED) with symptoms suggestive of acute coronary syndrome (ACS) varied on risk factors, comorbid conditions, functional status, and symptoms that have implications for emergent cardiac care. Women admitted to five EDs were enrolled. The ACS Symptom Checklist was used to measure symptoms. Comorbid conditions and functional status were measured with the Charlson Comorbidity Index and Duke Activity Status Index. Logistic regression models were used to evaluate symptom differences in older and younger women adjusting for ACS diagnosis, functional status, body mass index (BMI), and comorbid conditions. Analyses were stratified by age, and interaction of symptom by age was tested. Four hundred women were enrolled. Mean age was 61.3 years (range 21-98). Older women (n = 163) were more likely to have hypertension, hypercholesterolemia, never smoked, lower BMI, more comorbid conditions, and lower functional status. Younger women (n = 237) were more likely to be members of minority groups, be college-educated, and have a non-ACS discharge diagnosis. Younger women had higher odds of experiencing chest discomfort, chest pain, chest pressure, shortness of breath, nausea, sweating, and palpitations. Lack of chest symptoms and shortness of breath (key symptoms triggering a decision to seek emergency care) may cause older women to delay seeking treatment, placing them at risk for poorer outcomes. Younger African American women may require more comprehensive risk reduction strategies and symptom management

COMPARISON OF PLUG-IN GAIT AND A SIX DEGREES OF FREEDOM MODEL ON ESTIMATING KNEE KINEMATICS DURING A DOUBLE LEG DROP JUMP

Biomechanical models allow for a comprehensive understanding of dynamic movements that could be used to assess athletic performance or identify injury risk and return to play status. In order to make clinical recommendations based on these model outputs, discrepancies between modelling approaches need to be identified. The purpose of this study was to compare the knee kinematics between the commonly used Plug-in Gait model and a six degrees of freedom model during the first landing a double leg drop jump (DLDJ). This study identified differences in the model outputs for knee kinematics, most prominently in the frontal and transverse planes. Further investigation is required to determine the reliability and sensitivity of these model outputs

Perceptions of body weight that vary by body mass index: Clear associations with perceptions based on personal control and responsibility.

This project aimed to identify the perceptions of body weight that vary by body mass index. First, a qualitative study explored body weight perceptions in 17 individuals with overweight. Second, a questionnaire was developed and completed by a UK sample with body mass index from 16.6 to 59.7 kg/m2 (N = 328). A higher body mass index was associated with perceptions of less personal control and responsibility. Body mass index in females was also associated with three other questionnaire factors and body mass index in males with illness/medication. Thus, body mass index was associated with different perceptions of body weight. Focussing on personal control and responsibility may be useful for treatment and prevention

Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.

This paper was originally published in PLOS ONE (Robinson KA, Hegyi K, Hannun YA, Buse MG, Sethi JK, PLoS ONE 2014, 9(10): e108963. doi:10.1371/journal.pone.0108963).Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used "specific" inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not -β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway.This work was supported by grants from the Biotechnology and Biological Sciences Research Council (David Phillips Fellowship, JF16994), Diabetes UK (BDA:RD06/0003237) and British Heart Foundation (PG/10/38/28359) to J.K. Sethi and also from National Institute of Diabetes and Digestive and Kidney Diseases (DK-02001) to M.G. Buse

Combination treatment with zidovudine, didanosine, and nevirapine in infants with human immunodeficiency virus type 1 infection

BACKGROUND: In infants and children with maternally acquired human immunodeficiency virus type 1 (HIV-1) infection, treatment with a single antiretroviral agent has limited efficacy. We evaluated the safety and efficacy of a three-drug regimen in a small group of maternally infected infants. METHODS: Zidovudine, didanosine, and nevirapine were administered in combination orally to eight infants 2 to 16 months of age. The efficacy of antiretroviral treatment was evaluated by serial measurements of plasma HIV-1 RNA, quantitative plasma cultures, and quantitative cultures of peripheral-blood mononuclear cells. RESULTS: The three-drug regimen was well tolerated, without clinically important adverse events. Within four weeks, there were reductions in plasma levels of HIV-1 RNA of at least 96 percent (1.5 log) in seven of the eight study patients. Over the 6-month study period, replication of HIV-1 was controlled in two infants who began therapy at 2 1/2 months of age. Plasma RNA levels were reduced by 0.5 to 1.5 log in five of the other six infants. CONCLUSIONS: Although further observations are needed, it appears that in infants with maternally acquired HIV-1 infection, combined treatment with zidovudine, didanosine, and nevirapine is well tolerated and has sustained efficacy against HIV-1

Advancing Equity In The Pandemic Treaty

There is a broad consensus around equity’s importance. Even countries that hoarded supplies during the acute phase of COVID-19 seem to understand that the international community must find a means to ensure fairer allocation of medical resources when the next health crisis hits. But there has been little agreement about the concrete steps needed to operationalize fairer access and benefit sharing. That is, what are the workable mechanisms that could reduce the divide between richer and poorer populations? The World Health Assembly, the governing body of the World Health Organization, has appointed an Intergovernmental Negotiating Body to develop a pandemic convention, agreement, or other instrument under the WHO constitution. The February 2023 draft is designed “to achieve greater equity … through the fullest national and international cooperation.” It is important that the negotiators develop specific, measurable metrics that directly impact equity. The mechanisms and metrics agreed upon should allow the public to evaluate whether a more equitable system is emerging through this new regime. Equity won’t just happen. We need to plan and prepare for equity, and we need international norms with which nations must comply to achieve the fairness we strive for

A species-centered approach for uncovering generalities in organism responses to habitat loss and fragmentation

Theoretical models predict strong influences of habitat loss and fragmentation on species distributions and demography, but empirical studies have shown relatively inconsistent support across species and systems. We argue that species' responses to landscape-scale habitat loss and fragmentation are likely to appear less idiosyncratic if it is recognized that species perceive the same landscapes in different ways. We present a new quantitative approach that uses species distribution models (SDMs) to measure landscapes (e.g. patch size, isolation, matrix amount) from the perspective of individual species. First, we briefly summarize the few efforts to date demonstrating that once differences in habitat distributions are controlled, consistencies in species' responses to landscape structure emerge. Second, we present a detailed example providing step-by-step methods for application of a species-centered approach using freely available land-cover data and recent statistical modeling approaches. Third, we discuss pitfalls in current applications of the approach and recommend avenues for future developments. We conclude that the species-centered approach offers considerable promise as a means to test whether sensitivity to habitat loss and fragmentation is mediated by phylogenetic, ecological, and life-history traits. Cross-species generalities in responses to habitat loss and fragmentation will be challenging to uncover unless landscape mosaics are defined using models that reflect differing species-specific distributions, functional connectivity, and domains of scale. The emergence of such generalities would not only enhance scientific understanding of biotic processes driving fragmentation effects, but would allow managers to estimate species sensitivities in new regions.this study was supported by US National Science Foundation grants (NSF-ARC-0941748 and DEB-1050954